Process for preparing 4-hydroxy-6,7-substituted-3-carboalkoxyquinolines

ABSTRACT

4-Hydroxy-6,7-substituted-3-carboalkoxyquinolines, useful as coccidiostats, are readily prepared by refluxing a dimethyl sulfoxide solution of the corresponding 4-chloro compound.

United States Patent Harris [4 1 May 23, 1972 [54] PROCESS FOR PREPARING 4- HYDROXY-6,7-SUBSTITUTED-3- CARBOALKOXYQUINOLINES [72] Inventor: Nicholas D. Harris, Norwich, NY.

[73] Assignee: Morton-Norwich Products, Inc.

[22] Filed: Dec. 22, 1969 [21] Appl. No.: 887,386

[52] US. Cl. ..260/287 R [5 l Int. Cl. ..C07d 33/48 [58] Field ofSearch.. ..260/287,629

Primary Examiner-Donald G. Daus AttorneyBradford S. Allen ABSTRACT 4-Hydroxy-6,7-substituted-3-carboalkoxyquinolines, useful as coccidiostats, are readily prepared by refluxing a dimethyl sulfoxide solution of the corresponding 4-chloro compound.

1 Claim, No Drawings PROCESS FOR PREPARING 4-HYDROXY-6,7- SUBSTITUTED-3-CARBOALKOXYQUINOLINES This invention relates to a process for preparing 4-hydroxy- 6,7-substituted-3-carboalkoxyquinolines known to be useful as coccidiostats. More particularly it is concerned with the preparation of such quinolines wherein the 6,7-substituents are each alkoxy or one of them is alkoxy and the other alkyl. Still more particularly it aims to provide a process for preparing such quinolines which comprises heating a solution of the corresponding 4-chloro compound in dimethyl sulfoxide.

There is disclosed in US. Pat. No. 3,397,208 and British Pat. No. 1,138,539 a process for preparing 4-ch1oro-6,7-substituted-3-carboalkoxyquinolines by reacting a dialkyl 3,4- substituted anilinomethylenemalonate with phosphorus oxychloride followed by acid hydrolysis to secure the corresponding 4-hydroxy compounds which are useful coccidiostats.

The instant invention provides an alternative, simple and inexpensive method for converting 4-chloro-6,7-substituted-3- carboalkoxyquinolines to the respective 4-hydroxy counterparts. in accordance with this invention the 4-chloro-6,7-substituted-3-carboalkoxyquinoline is dissolved in dimethyl sulfoxide and the resultant solution heated. Following the heating period the solution is quenched and the 4-hydroxy-6,7-substituted-3-carboalkoxyquinoline recovered.

In order that this invention may be readily available to and understood by those skilled in the art the following illustrative examples are supplied:

EXAMPLE I Ethyl 4 ch1oro-6,7-diisobutoxy-3-quinolinecarboxylate (5 g.) and dimethyl sulfoxide (40 ml.) were heated on the steam bath for 2 hours. The reaction mixture was cooled to 20C. The solid was collected, washed with dimethyl sulfoxide and dried to yield (80 percent) ethyl 4-hydroxy-6,7-diisobutoxy-3- quinolinecarboxylate (mp. 282-284C.

EXAMPLE 2 Ethyl 6-decyloxy-7-ethoxy-4-chloro-3-quinolinecarboxylate (0.5 g.), mp 8687C., and dimethyl sulfoxide (7 ml.) were heated at for 2 hours. The reaction mixture was cooled and the solid was collected, washed with n-hexane, and dried at 100 to yield 0.35 g. of ethyl 4-hydroxy-6-decyloxy-7-ethoxy-3-quinolinecarboxylate (mp. 246-248").

EXAMPLE 3 wherein R is isobutoxy, decyloxy or n-butyl; R is isobutoxy, ethoxy or benzyloxy; and R is methyl or ethyl which consists in heating a compound of the formula:

31 n- VCOOIh R. N

wherein R, R and R have the aforeassigned significance in the presence of dimethy lsul foxlde mm" n10 

